Succinate forms and compositions of Bruton's tyrosine kinase inhibitors
View Patent ↗The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
1. A solid form Compound 2 comprising Compound 1 and succinic acid:
2. The solid form of claim 1 , wherein said solid form is a crystalline solid.
3. The solid form of claim 2 , wherein said solid form is Form 1.
4. The solid form of claim 3 , having one or more peaks in its X-ray powder diffraction pattern at about 5.33, about 7.59, about 9.75, about 13.69, about 17.91, about 18.14, about 20.12, or about 24.73 degrees 2-theta.
5. The solid form of claim 4 , having a XRPD substantially similar to that depicted in FIG. 1 .
6. The solid form of claim 2 , wherein said compound is Form 2.
7. The solid form of claim 6 , having one or more peaks in its X-ray powder diffraction pattern at about 6.76, about 8.77, about 9.06, about 12.00, about 13.53, about 18.13, or about 20.07 degrees 2-theta.
8. The solid form of claim 7 , having a XRPD substantially similar to that depicted in FIG. 5 .
9. The solid form of claim 1 , wherein said solid form is an amorphous solid form.
10. A composition comprising the solid form of claim 1 and a pharmaceutically acceptable carrier or excipient.
11. A method of treating a disorder responsive to inhibition of Bruton's tyrosine kinase comprising administering to a subject an effective amount of the solid form of claim 1 or a composition thereof, wherein the disorder is selected from chronic lymphocytic leukemia, acute lymphocytic leukemia, diffuse Large B-cell lymphoma, rheumatoid arthritis, non-Hodgkin lymphoma, and Waldönstrom's macroglobulinemia.
12. A method of treating a disorder selected from chronic lymphocytic leukemia, acute lymphocytic leukemia, diffuse Large B-cell lymphoma, rheumatoid arthritis, non-Hodgkin lymphoma, and Waldönstrom's macroglobulinemia comprising administering to a subject an effective amount of the solid form of claim 1 or a composition thereof.
13. The method of claim 12 , wherein the effective amount of a solid form or a composition thereof is about 25 mg to about 300 mg.
14. The method of claim 13 , wherein the solid form or composition thereof, is administered once, twice, or more than twice daily.
15. A unit dosage form of the solid form of claim 1 and a pharmaceutically acceptable carrier or excipient.
16. The unit dosage form of claim 15 , comprising an amount of Compound 2 that is about 25 mg to about 300 mg.
17. An oral formulation comprising the solid form of claim 1 and a pharmaceutically acceptable carrier or excipient.
18. A method of treating a subject having a disorder responsive to inhibition of BTK, in which the subject has been treated with a first BTK inhibitor and has acquired a functional BTK Cys481 mutation that impairs the activity of the first BTK inhibitor, comprising administering to the subject an effective amount of Compound 1, a solid form of claim 1 , or a composition thereof, wherein the disorder is selected from chronic lymphocytic leukemia, acute lymphocytic leukemia, diffuse Large B-cell lymphoma, rheumatoid arthritis, non-Hodgkin lymphoma, and Waldönstrom's macroglobulinemia.
19. The method of claim 18 , wherein the mutation is C481S, C481F, C481G, or C481T.